Relationship of dietary and serum zinc and leptin levels with protein energy wasting in haemodialysis patients.

Effects of zinc supplementation on serum zinc and leptin levels, BMI, and body composition in hemodialysis patients

Objective The aim of this study was to determine the effect of zinc supplementation on serum levels of zinc and leptin in pediatric patients on hemodialysis (HD). Background Zinc is an essential trace element for human nutrition, and its deficiency which could result in anorexia, poor nutritional status, high rates of infections, and growth retardation. Many patients on maintenance HD exhibit zinc deficiency. Leptin may offer a tool for making clear the physiology of zinc deficiency–induced anorexia based on a relationship between zinc and leptin levels. Patient and methods The study was carried out on 42 children divided into two groups: group I included 22 children on HD who received 50-mg zinc gluconate twice daily for 90 days, and group II included healthy children as controls. Anthropometric measurements were taken, and serum zinc and leptin levels were determined the day before supplementation and at day 90 of the study. Results Serum level of zinc is decreased and serum leptin level is increased in children on regular HD. There is an increase in zinc level and a decrease in serum leptin level after zinc supplementation. Conclusion Zinc supplementation increased serum zinc level and decreased serum leptin level among males and females in the studied patients. Enhancement of serum zinc level improves appetite and stimulate food intake.

IntroductionZinc is an essential trace element for human nutrition, and its deficiency is associated with anorexia, poor food efficiency, growth retardation, and impaired neurological and immune systems. The zinc-deficiency rate is particularly high in many disease states, such as with end-stage renal disease patients undertaking hemodialysis. The aim of this study was to determine the effect of zinc supplementation on body mass index (BMI) and serum levels of zinc and leptin in pediatric hemodialysis patients.Patients and methodsThis was a prospective clinical trial study in which 60 hemodialysis patients were randomly divided into two groups: group I received 50–100 mg zinc sulfate (equivalent to 11–22 mg elemental zinc) according to age, sex, and nutritional status of the child; and group II received placebo (cornstarch) twice daily for 90 days. Anthropometric measurements were taken, and serum zinc and leptin levels were determined by colorimetric test with 5-Br-3′-phosphoadenosine-5′-phosphosulfate and enzyme-linked immunosorbent assay, respectively, at days 0 and 90 of the study.ResultsZinc supplementation resulted in a significant increase in mean serum zinc level and BMI. Serum leptin decreased significantly after supplementation in children under hemodialysis. A significant negative correlation was observed between serum zinc and leptin levels as a result of zinc supplementation.ConclusionThere was an increase in serum zinc level and BMI and decreased serum leptin after zinc supplementation in children under hemodialysis.

Serum leptin and lipoprotein levels in women with PCOS.

P-28: The utility of serum leptin and follicular fluid leptin, estradiol, and progesterone concentrations in infertility patients undergoing in vitro fertilization

Issue Highlights

Sir, Leptin is a peptide hormone produced by the ob gene of adipocytes1. In experimental animals hyperleptinemia increases insulin resistance and hepatic triglyceride content which may lead to hepatic steatosis and steatohepatitis. This suggests that leptin may have a role in the aetiopathogenesis of non-alcoholic steatohepatitis (NASH)1,2,3,4. Leptin levels in NASH patients have been studied in western population. We therefore, measured serum leptin levels in Indian patients and correlated it with their body mass index (BMI) and histologic features in patients with NASH. The aims of this study were to compare serum leptin levels in patients with NASH and matched controls, and to correlate serum leptin levels with clinical, biochemical and histological features to elucidate the role of leptin in the pathogenesis of NASH. Inclusion criteria were elevated alanine aminotransferase (ALT) levels more than 1.5 times normal for >6 months, alcohol intake <20 g/day, fatty liver on ultrasonography (USG) or MRI, and adequate liver biopsy for histological examination. Patients were excluded if they had any systemic illness, were taking any medication like estrogens, methotrexate, corticosteroids, tamoxifen and amiodarone in the last one year, were following any dietary regimen or receiving any treatment for NASH. Twenty one consecutive patients presenting to Gastrointestinal out-patient department of our hospital from January 2009 to March 2009 and an equal number of age, sex and BMI matched controls (recruited from the staff of the hospital) were included in the study. Chronic liver disease was excluded in controls by physical examination, viral serology and abdominal USG scan. In the patients, anthropometric data were recorded and laboratory tests were done to exclude viral and autoimmune aetiology. Serum leptin was measured by enzyme linked immunosorbant assay kit (Titerzyme EIA, ELISA kit, Assay designs’ Inc, USA). Liver biopsies were graded and staged according to the criteria given by Brunt et al5. The mean age of the patients was 31 ± 7 yr and mean BMI was 25.1 ± 1.2 kg/m2. One patient had diabetes mellitus, 19 had hypertriglyceridaemia, and 11 had insulin resistance (Table). Serum leptin was significantly (P<0.05) higher in NASH patients compared to controls. On univariate analysis, BMI (r = 0.934, P<0.001), necroinflammatory activity (P=0.019) and fibrosis stage (P=0.042) correlated with serum leptin levels. On multivariate regression analysis, BMI was the only independent predictor of serum leptin levels (P<0.001). On univariate analysis, serum leptin levels (P=0.047), BMI (P=0.004), serum ALT levels (P=0.012), steatosis (P=0.001) and lobular inflammation (P=0.005) correlated with necroinflammatory grade of NASH. On multivariate regression analysis only ALT levels (P=0.027) and lobular inflammation (P=0.038) were independent predictor of necroinflammatory grade. Further multivariate regression analysis did not show leptin to be an independent predictor of steatosis, lobular inflammation, portal inflammation or fibrosis. Table Anthropometric and biochemical parameters of patients with NASH and matched controls Our study confirmed the earlier findings6,7 reporting significantly higher serum leptin levels in patients with NASH as compared to controls. In our study serum leptin levels showed disproportionately greater increase with BMI in NASH patients as compared to matched controls. Thus, the increases in leptin levels in NASH is not explained by obesity alone but is also due to peripheral leptin resistance. In NASH leptin receptors become resistant to its effect leading to hyperleptinemia which alters insulin signaling and promotes accumulation of intracellular fatty acids in hepatocytes thereby increasing hepatic steatosis and steatohepatitis7,8,9,10,12. Our study indicates that serum leptin increases the severity of necroinflammation and fibrosis in NASH but it is not an independent predictor of disease severity. In our study serum leptin was not found to be an independent predictor of liver fibrosis. Chitturi et al6 (47 patients) and Chalasani et al10 (26 patients) also did not find any correlation between serum leptin levels and fibrosis stage. Kim et al11 found that serum leptin levels correlated with hepatic fibrosis, but serum leptin was not an independent predictor on univariate analysis. In conclusion, this study suggests that serum leptin levels are increased in NASH patients disproportionate to increase in BMI, however, leptin levels do not predict histologic severity of NASH (necroinflammation or fibrosis) on liver biopsy. Further studies are needed to determine clearly the role of leptin and other adipokines in causing hepatic steatosis and steatohepatitis.

A proposed nomenclature and diagnostic criteria for protein–energy wasting in acute and chronic kidney disease

Chronic inflammation is prevalent in dialysis patients. We investigated the relationship between inflammation and newly identified adipokines: leptin and adiponectin in this population. A total of 129 chronic hemodialysis patients were collected. Serum high sensitivity C-reactive protein (CRP), interleukin-6 (IL-6), leptin and adiponectin levels were determined as well as other metabolic variables. Correlation studies and multiple regression analysis were performed among variables. Our results showed that hemodialysis patients had elevated levels of inflammatory markers, leptin and adiponectin. Diabetic subjects had higher serum CRP and lower albumin levels than non-diabetics. Serum CRP levels were positively correlated with IL-6 levels and negatively correlated with albumin levels. Serum leptin levels were directly related to CRP levels while adiponectin levels were inversely related to CRP levels. A significant negative correlation was observed between serum leptin and adiponectin levels. Serum IL-6 levels were the single independent factor affecting CRP levels. Body mass index can predict both serum leptin and adiponectin levels. We conclude that hemodialysis patients are at an increased risk of chronic inflammation and diabetes patients are even more susceptible to this status. Both serum leptin and adiponectin levels are associated with inflammatory markers. As adipose tissue is the major secreting site of these adipokines, our results suggest that adipose tissue plays an important role in the pathogenesis of chronic inflammation in dialysis patients.

Secretion of insulin is compromised in type 2 diabetes (T2DM) individuals and inadequate to accommodate for insulin resistance (IR) in peripheral tissue. Hyperleptinemia reflects leptin resistance, which is a key factor in the production of IR in T2DM patients, making leptin a potential biomarker for evaluating IR levels. The objective of the study was to assess the association of serum leptin and insulin levels among T2DM patients. This case-control research was carried out on T2DM patients. A total of 73 patients diagnosed with T2DM (the case group) and 40 healthy participants (control; group 3) were enrolled according to the American Diabetes Association (ADA) criteria. In the case group, T2DM patients were enrolled with metabolic syndrome (group 1, n = 38) or without metabolic syndrome (group 2, n = 35) according to the WHO criteria. Metabolic profiles of T2DM patients with or without metabolic syndrome were evaluated, and compare these two groups with healthy controls. The subjects of all groups were age- and gender-matched. Body mass index (BMI, P < .01), fasting (P = .0133) and postprandial (P < .01) blood sugar levels, % glycated hemoglobin (HbA1c, P < .01), and lipid profile (P < .01) were found significantly different and higher in group 1 as compared to groups 2 and 3. Serum leptin and insulin levels were found higher and significant in patients with metabolic syndrome (P < .01 for both). The values of serum leptin levels were 10.01 ± 2.7 ng/mL, 6.9 ± 2.4 ng/mL, and 4.11 ± 1.8 ng/mL, and those of serum insulin 120 ± 40.7 µIU/mL, 20.43 ± 5.2 µIU/mL, and 11.4 ± 2.5 µIU/mL in groups 1, 2, and 3, respectively. There was a positive linear correlation between BMI, blood sugar, HbA1c, serum cholesterol (TC), and triglycerides (TG) with serum insulin and leptin levels in the case group. An extremely significant correlation (R = 0.74, P < .001) was found in BMI and serum leptin level in the case group. Serum leptin and insulin levels have a positive association, with serum leptin being a significant predictor of IR syndrome (Evidence Level: 5; Technical Efficacy: Stage 3).

Leptin may contribute to renal pathology in some situations by stimulating transforming growth factor-beta1 (TGF-beta1) synthesis. The soluble leptin receptor (sOb-R) is a transport protein contributing to binding and activation of circulating leptin. We investigated the interaction between serum and urinary leptin, TGF-beta1, and serum sOb-R levels in 38 patients with minimal change nephrotic syndrome (MCNS) aged between 6 and 12 years and 10 age- and sex-matched healthy controls (group III). Patients were divided into two groups: group I, proteinuria exceeding >40 mg/m(2) per hour and group II, patients in remission. Serum leptin levels in group I were significantly lower than those in group II and group III ( P=0.011, P=0.007, respectively). There was a negative correlation between serum leptin levels and proteinuria ( r=-0.52, P=0.02) as well as between serum leptin and sOb-R levels ( r=-0.82, P=0.000) in group I. Urine leptin and sOb-R levels in group I were significantly higher than in group II ( P=0.0021, P=0.001, respectively) and group III ( P=0.07, P=0.009, respectively). Serum TGF-beta1 levels in healthy controls (406+/-424 pg/ml) were significantly lower than those in groups I and II ( P=0.004, P=0.000, respectively). However, no significant correlation was found between the serum TGF-beta1 and leptin levels in MCNS patients. In conclusion, low serum leptin, high serum TGF-beta1 and sOb-R levels, and elevated urine leptin concentrations were observed at the onset of MCNS. Since long-term proteinuria and leptinuria might be associated with the progression of renal damage, future in vivo and in vitro studies are needed to explain the interaction between these parameters in different types of nephrotic syndrome.

Weight gain is a common adverse effect associated with the use of most antipsychotic drugs. Leptin has been reported to be associated with antipsychotic-induced weight gain. Previous studies have demonstrated a relationship between the atypical antipsychotics clozapine and olanzapine and serum leptin levels. We planned to comparatively investigate the effects of the atypical antipsychotics quetiapine, olanzapine, risperidone, and clozapine on leptin and triglyceride levels and weight gain. The study population comprised 56 patients with DSM-IV schizophrenia, who were divided into 4 treatment groups: quetiapine (N = 14), olanzapine (N = 14), risperidone (N = 14), or clozapine (N = 14) monotherapy, and a control group of 11 patients receiving no psychopharmacologic treatment. The patients were evaluated at baseline and at the sixth week according to the Positive and Negative Syndrome Scale (PANSS), body mass index (BMI), weight, and fasting serum leptin and triglyceride levels. Data were gathered in 2001 and 2002. Olanzapine and clozapine caused a marked increase in weight and serum triglyceride and leptin levels, though increases in these variables were modest in the patients receiving quetiapine and minimal in those receiving risperidone. There were positive correlations between serum leptin levels and BMI and triglyceride levels. Clinical efficacy, as indicated by decrease in total PANSS scores, was associated with leptin levels in all atypical antipsychotic groups. Our results suggest that leptin may be associated with olanzapine- and clozapine-induced weight gain and that quetiapine appears to have modest influence and risperidone appears to have minimal influence on leptin and triglyceride levels and weight gain compared with olanzapine and clozapine.

BackgroundPlasma leptin is considered a risk factor for obesity and cardio-metabolic disease, but the link between serum leptin and renal function is still under evaluation. In our study, we focused on the relationship between serum leptin and renal function, and we investigated the relationship in more detail.MethodsThe 396 middle-aged and elderly Taiwanese adults recruited for our health survey were the subject of our research. All participants agreed to participate and signed a consent form before they joined and completed our study. We divided the participants into three groups according to eGFR tertiles and analyzed the parameters between each group. Then, we used Pearson’s correlation test to investigate the relationship between eGFR levels and cardio-metabolic risk factors with adjustment for age. The scatter plot indicates the trend between serum leptin levels and eGFR levels. Participants were reclassified into three subgroups according to their leptin levels and the bar chart reveals the prevalence of chronic kidney disease (CKD) in each group. Finally, we used multivariate linear regression to evaluate the relationship between serum leptin and eGFR levels with adjustment for age, sex, smoking status, drinking status, body mass index (BMI), uric acid levels, hypertension (HTN), diabetes mellitus (DM), and dyslipidemia.ResultsIn our study, we analyzed the data from 396 eligible participants. A total of 41.4% of the participants were male, and the average age of all participants was 64.81 years ( ± 8.78). The participants in the high eGFR group were more likely to have lower serum leptin levels. Furthermore, eGFR values were negatively correlated with serum leptin levels even after adjustment for age. The prevalence of CKD in the high serum leptin group was higher than that in the low serum leptin group. Serum leptin levels showed significant negative correlations with eGFR levels (β=-0.14, p<0.01) in the multivariate linear regression after adjusting for age, sex, smoking status, drinking status, BMI, uric acid levels, HTN, DM, and dyslipidemia.ConclusionAccording to our study, serum leptin levels show a negative relationship with eGFR levels in middle-aged and elderly people in Taiwan. In addition, high serum leptin levels could be an novel marker to survey kidney failure in clinical practices.

Leptin is a 16 kDa protein hormone involved in food intake, energy expenditure regulation and numerous other physiological processes. Recently, leptin has been demonstrated to stimulate hematopoietic stem cells in vitro. The aim of our study was to measure serum leptin and erythropoietin levels in patients with sideropenic (n =18) and pernicious anemia (n=7) before and during anemia treatment. Blood samples for the blood count, leptin and erythropoietin determinations were obtained by venepunction at the time of the diagnosis of anemia and after partial and complete anemia recovery. The relationships of serum leptin levels to erythropoietin levels and blood count parameters were also studied. No significant differences in serum leptin levels between the groups studied were found. The serum leptin levels in none of groups were modified by treatment of anemia (basal levels, the levels during treatment and after anemia recovery were 13.1±14.5 vs 12.8±15.6 vs 12.0±14.8 ng/ml in patients with sideropenic anemia and 7.8±8.5 vs 9.5±10.0 vs 8.9±6.6 ng/ml in patients with pernicious anemia). The erythropoietin levels were higher at the time of anemia in both groups and decreased significantly after partial or complete recovery. Serum leptin levels in both groups correlated positively with the body mass index. No significant relationships were found between serum leptin levels and erythropoietin values or various parameters of the peripheral blood count. We conclude that serum leptin levels in patients with sideropenic and pernicious anemia positively correlate with the body mass index but are not influenced by the treatment of anemia.

The enigma of increasing serum leptin levels during peritoneal dialysis.